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Dose‐response curves of histamine‐ and allergen‐induced wheal areas were evaluated in seven normals (defined as negative skin prick test (SPT) to inhalant allergens and no clinical signs of allergy), seven latent allergies (positive SPT without allergic symptoms), and 20 manifest allergies (positive SPT and allergic symptoms). Three concentrations of histamine HCl (1, 10 and 100 mg/ml) and three 10‐fold concentrations of nine inhalant allergens (birch, timothy, mugwort, horse, dog, cat, house dust mite, Cladosporium and Alternaria) in concentrations 1,000 10,000 and 100,000 BU/ml were used and linear regression was performed on the skin reactions. Only tests with an SD% < 40%, a log slope > 0.1, and a correlation coefficient > 0.95 were accepted. In normals a significantly higher concentration of histamine was needed to elicit a wheal reaction of 2 mm2 (end‐point) compared with allergies. Likewise, normals had a significantly higher slope i.e. steeper dose‐response curve of histamine than manifest allergies. The slope of the allergen‐induced wheal area was significantly higher than the histamine slope. No relation between corresponding slope of histamine and allergens was found (Rho = 0.15). The skin sensitivity equivalent to histamine calculated as the allergen concentration eliciting a wheal equal to histamine showed a median increase of 5–6 fold in allergen concentration by a 10‐fold increase of histamine concentration. The highest correlation between the wheal area of a single allergen concentration and the skin sensitivity was found for allergen concentration 100,000 BU. Based on these results it is recommended that biological standardization of allergen extracts is based on quantitative skin titration of at least three 10‐fold concentrations of both histamine and allergens and the biological activity (HEP unit) re‐defined from histamine HCl 10 mg/ml.
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